TY  - JOUR
AU  - Miler, Marko
AU  - Živanović, Jasmina
AU  - Ajdžanović, Vladimir
AU  - Milenkovic, Dragan
AU  - Cesar, Thais
AU  - Filipović R., Miloš
AU  - Milošević, Verica
PY  - 2024
UR  - https://iubmb.onlinelibrary.wiley.com/journal/18728081
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6462
AB  - Citrus flavanones are recognized as promising bioactives within the concept of healthy aging. Thus, the present study investigated the effects of a nutritionally relevant dose of lemon extract (LE) on liver redox regulation and persulfidation levels in 24-month-old Wistar rats. LE (40 mg/kg b.m.) was administered orally once daily for four weeks. Control groups received either vehicle (sunflower oil) or remained intact. The applied methodology considered qPCR, Western blot, protein persulfidation levels evaluation, histochemistry in line with immunofluorescence, liver biochemical assays (glutathione, total -SH groups and malonaldehyde; MDA), liver enzymes in serum and in silico analysis to explore the potential interaction/binding between the proteins studied in the paper. Our results showed that LE increased glutathione peroxidase (GPx), reductase (GR), glutamate-cysteine ligase catalytic and modifier subunit, respectively, as well as Nrf2 gene expressions, but decreased the expression of superoxide dismutase 2 (SOD2). Upon LE application, protein expression showed upregulation of NRF2, SOD2, GPx, GR, and thioredoxin 1 (Trx1). LE significantly decreased the protein persulfidation levels and concentration of MDA, a marker of oxidative damage in the cell. Histological analysis showed a normal liver histoarchitecture without pathological changes, aligning with the normal serum level of hepatic enzymes. Obtained results showed that LE, by modulating hepatic redox regulators Nrf2 and Trx1, diminishes oxidative stress and alters the persulfidation levels, suggesting a considerable beneficial antioxidant potential of lemon flavanones in the old-aged liver.
PB  - John Wiley and Sons
T2  - Biofactors
T1  - Lemon extract reduces the hepatic oxidative stress and persulfidation levels by upregulating the Nrf2 and Trx1 expression in old rats
DO  - 10.1002/biof.2038
ER  - 

@article{
author = "Miler, Marko and Živanović, Jasmina and Ajdžanović, Vladimir and Milenkovic, Dragan and Cesar, Thais and Filipović R., Miloš and Milošević, Verica",
year = "2024",
abstract = "Citrus flavanones are recognized as promising bioactives within the concept of healthy aging. Thus, the present study investigated the effects of a nutritionally relevant dose of lemon extract (LE) on liver redox regulation and persulfidation levels in 24-month-old Wistar rats. LE (40 mg/kg b.m.) was administered orally once daily for four weeks. Control groups received either vehicle (sunflower oil) or remained intact. The applied methodology considered qPCR, Western blot, protein persulfidation levels evaluation, histochemistry in line with immunofluorescence, liver biochemical assays (glutathione, total -SH groups and malonaldehyde; MDA), liver enzymes in serum and in silico analysis to explore the potential interaction/binding between the proteins studied in the paper. Our results showed that LE increased glutathione peroxidase (GPx), reductase (GR), glutamate-cysteine ligase catalytic and modifier subunit, respectively, as well as Nrf2 gene expressions, but decreased the expression of superoxide dismutase 2 (SOD2). Upon LE application, protein expression showed upregulation of NRF2, SOD2, GPx, GR, and thioredoxin 1 (Trx1). LE significantly decreased the protein persulfidation levels and concentration of MDA, a marker of oxidative damage in the cell. Histological analysis showed a normal liver histoarchitecture without pathological changes, aligning with the normal serum level of hepatic enzymes. Obtained results showed that LE, by modulating hepatic redox regulators Nrf2 and Trx1, diminishes oxidative stress and alters the persulfidation levels, suggesting a considerable beneficial antioxidant potential of lemon flavanones in the old-aged liver.",
publisher = "John Wiley and Sons",
journal = "Biofactors",
title = "Lemon extract reduces the hepatic oxidative stress and persulfidation levels by upregulating the Nrf2 and Trx1 expression in old rats",
doi = "10.1002/biof.2038"
}

Miler, M., Živanović, J., Ajdžanović, V., Milenkovic, D., Cesar, T., Filipović R., M.,& Milošević, V.. (2024). Lemon extract reduces the hepatic oxidative stress and persulfidation levels by upregulating the Nrf2 and Trx1 expression in old rats. in Biofactors
John Wiley and Sons..
https://doi.org/10.1002/biof.2038

Miler M, Živanović J, Ajdžanović V, Milenkovic D, Cesar T, Filipović R. M, Milošević V. Lemon extract reduces the hepatic oxidative stress and persulfidation levels by upregulating the Nrf2 and Trx1 expression in old rats. in Biofactors. 2024;.
doi:10.1002/biof.2038 .

Miler, Marko, Živanović, Jasmina, Ajdžanović, Vladimir, Milenkovic, Dragan, Cesar, Thais, Filipović R., Miloš, Milošević, Verica, "Lemon extract reduces the hepatic oxidative stress and persulfidation levels by upregulating the Nrf2 and Trx1 expression in old rats" in Biofactors (2024),
https://doi.org/10.1002/biof.2038 . .

TY  - CONF
AU  - Živanović, Jasmina
AU  - Kouroussis, Emilia
AU  - Kohl, Joshua
AU  - Miler, Marko
AU  - Mitchell, Sarah
AU  - Mitchell, James
AU  - Schwartz, Guenter
AU  - Milošević, Verica
AU  - Filipović R., Miloš
PY  - 2019
UR  - https://www.bcp.fu-berlin.de/en/biologie/arbeitsgruppen/mikrobiologie/ag_antelmann/meetings/190915_redox_res/Flyer-Sant-Feliu-2019-final6.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6039
AB  - For couple of decades aging is believed to be a consequence of damages accumulated by increased production of reactive oxygen species (ROS). Opposite to that, dietary restriction attempts to extend life have been linked to increased H2S production. We hypothesized that reacting with sulfenic acids (formed by ROS) H2S would rescue cysteine residue by forming persulfides. Persulfides are better ROS scavengers and could form protein S-sulfonates that could be cleaved back by disulfide reductase to restore free thiolate. This rescue loop would thus prevent irreversible thiol hyperoxidation. Using dimedone switch method we could first show that persulfidation is a posttranslational modification that is evolutionarily conserved (bacteria, flies, worms, mice and humans). Then we could also observe that thioredoxin readily catalyzes the reduction of cysteine S-sulfonate, two orders of magnitude faster than the reduction of corresponding disulfide. The persulfidation levels/H2S producing ability positively correlated with the ability of yeast, worms and mammalian cells to resist stress caused by ROS. Persulfidation declines with aging in worms, rats and mice, due to the downregulation of H2S producing enzymes, but dietary restriction in mice and worms restores persulfide levels and improves their lifespan. Based on these data we suggest that persulfidation represents an evolutionarily conserved anti-aging mechanism.
PB  - Berlin: Freie Universität Berlin
C3  - SPP1710 Conference: Thiol-based switches and redox regulation - from microbes to men; 2019 Sep 15-20; Sant Feliu de Guixols, Spain
T1  - Protein Persulfidation Protects Against Aging
SP  - 169
EP  - 169
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6039
ER  - 

@conference{
author = "Živanović, Jasmina and Kouroussis, Emilia and Kohl, Joshua and Miler, Marko and Mitchell, Sarah and Mitchell, James and Schwartz, Guenter and Milošević, Verica and Filipović R., Miloš",
year = "2019",
abstract = "For couple of decades aging is believed to be a consequence of damages accumulated by increased production of reactive oxygen species (ROS). Opposite to that, dietary restriction attempts to extend life have been linked to increased H2S production. We hypothesized that reacting with sulfenic acids (formed by ROS) H2S would rescue cysteine residue by forming persulfides. Persulfides are better ROS scavengers and could form protein S-sulfonates that could be cleaved back by disulfide reductase to restore free thiolate. This rescue loop would thus prevent irreversible thiol hyperoxidation. Using dimedone switch method we could first show that persulfidation is a posttranslational modification that is evolutionarily conserved (bacteria, flies, worms, mice and humans). Then we could also observe that thioredoxin readily catalyzes the reduction of cysteine S-sulfonate, two orders of magnitude faster than the reduction of corresponding disulfide. The persulfidation levels/H2S producing ability positively correlated with the ability of yeast, worms and mammalian cells to resist stress caused by ROS. Persulfidation declines with aging in worms, rats and mice, due to the downregulation of H2S producing enzymes, but dietary restriction in mice and worms restores persulfide levels and improves their lifespan. Based on these data we suggest that persulfidation represents an evolutionarily conserved anti-aging mechanism.",
publisher = "Berlin: Freie Universität Berlin",
journal = "SPP1710 Conference: Thiol-based switches and redox regulation - from microbes to men; 2019 Sep 15-20; Sant Feliu de Guixols, Spain",
title = "Protein Persulfidation Protects Against Aging",
pages = "169-169",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6039"
}

Živanović, J., Kouroussis, E., Kohl, J., Miler, M., Mitchell, S., Mitchell, J., Schwartz, G., Milošević, V.,& Filipović R., M.. (2019). Protein Persulfidation Protects Against Aging. in SPP1710 Conference: Thiol-based switches and redox regulation - from microbes to men; 2019 Sep 15-20; Sant Feliu de Guixols, Spain
Berlin: Freie Universität Berlin., 169-169.
https://hdl.handle.net/21.15107/rcub_ibiss_6039

Živanović J, Kouroussis E, Kohl J, Miler M, Mitchell S, Mitchell J, Schwartz G, Milošević V, Filipović R. M. Protein Persulfidation Protects Against Aging. in SPP1710 Conference: Thiol-based switches and redox regulation - from microbes to men; 2019 Sep 15-20; Sant Feliu de Guixols, Spain. 2019;:169-169.
https://hdl.handle.net/21.15107/rcub_ibiss_6039 .

Živanović, Jasmina, Kouroussis, Emilia, Kohl, Joshua, Miler, Marko, Mitchell, Sarah, Mitchell, James, Schwartz, Guenter, Milošević, Verica, Filipović R., Miloš, "Protein Persulfidation Protects Against Aging" in SPP1710 Conference: Thiol-based switches and redox regulation - from microbes to men; 2019 Sep 15-20; Sant Feliu de Guixols, Spain (2019):169-169,
https://hdl.handle.net/21.15107/rcub_ibiss_6039 .

TY  - CONF
AU  - Živanović, Jasmina
AU  - Kouroussis, Emilia
AU  - Miler, Marko
AU  - Schott-Roux, Sonia
AU  - Jarić, Ivana
AU  - Jakovljević, Vladimir
AU  - Milošević, Verica
AU  - Filipović R., Miloš
PY  - 2018
UR  - http://physiology.org.rs/4thCPS.php
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5926
AB  - An oxidative-posttranslational modification of thiols called protein persulfidation
(RSSH) represents the underlying mechanism of biological actions ascribed to new gasotransmitter hydrogen sulfide (H2S). We developed a new dimedone based method for detection of protein persulfidation and its selectivity was tested and confirmed in various experimental models (D. melanogaster, C. elegans, M. musculus. human cell lines and samples). Obtained results demonstrated that persulfidation represents an evolutionary conserved modification that correlates to the H2S production capacity and is accompanied with numerous physiological implications. One of such general observations is that persulfidation represents protective mechanism for the reduction of sulfenic acids under conditions of oxidative stress. When C. elegans mutants for CSE and MST were exposed to different oxidative stress inducers they showed enhanced sensitivity, while pretreatment with H2S donors rescued them. Additionally, we observed a strong correlation between protein persulfidation levels and development and aging in different experimental models. Fluctuations in the level of persultides were observed during development of C. elegans with prominent increase in L3 larval stage. Our data showed that after strong peak in L3, persulfide levels decreases during life in C. elegans. Decline of persulfide levels in the adult worms of different age was also observed. Similar effect was discovered in the brains of rats of different age. Immunobistological analysis of brain sections for H2S producing enzymes revealed the decrease in intensity of immunopositivity during aging process. Our results strongly propose protein persullidation represents a rescue loop from cysteine hyper-oxidation and subsequent loss of protein function. This general mechanism represents a promising tool in overcoming the consequences of increased oxidative stress during aging process.
PB  - Belgrade: Serbian Physiological Society
C3  - Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences : from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia
T1  - Anti-aging properties of protein persulfidation
SP  - 143
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5926
ER  - 

@conference{
author = "Živanović, Jasmina and Kouroussis, Emilia and Miler, Marko and Schott-Roux, Sonia and Jarić, Ivana and Jakovljević, Vladimir and Milošević, Verica and Filipović R., Miloš",
year = "2018",
abstract = "An oxidative-posttranslational modification of thiols called protein persulfidation
(RSSH) represents the underlying mechanism of biological actions ascribed to new gasotransmitter hydrogen sulfide (H2S). We developed a new dimedone based method for detection of protein persulfidation and its selectivity was tested and confirmed in various experimental models (D. melanogaster, C. elegans, M. musculus. human cell lines and samples). Obtained results demonstrated that persulfidation represents an evolutionary conserved modification that correlates to the H2S production capacity and is accompanied with numerous physiological implications. One of such general observations is that persulfidation represents protective mechanism for the reduction of sulfenic acids under conditions of oxidative stress. When C. elegans mutants for CSE and MST were exposed to different oxidative stress inducers they showed enhanced sensitivity, while pretreatment with H2S donors rescued them. Additionally, we observed a strong correlation between protein persulfidation levels and development and aging in different experimental models. Fluctuations in the level of persultides were observed during development of C. elegans with prominent increase in L3 larval stage. Our data showed that after strong peak in L3, persulfide levels decreases during life in C. elegans. Decline of persulfide levels in the adult worms of different age was also observed. Similar effect was discovered in the brains of rats of different age. Immunobistological analysis of brain sections for H2S producing enzymes revealed the decrease in intensity of immunopositivity during aging process. Our results strongly propose protein persullidation represents a rescue loop from cysteine hyper-oxidation and subsequent loss of protein function. This general mechanism represents a promising tool in overcoming the consequences of increased oxidative stress during aging process.",
publisher = "Belgrade: Serbian Physiological Society",
journal = "Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences : from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia",
title = "Anti-aging properties of protein persulfidation",
pages = "143",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5926"
}

Živanović, J., Kouroussis, E., Miler, M., Schott-Roux, S., Jarić, I., Jakovljević, V., Milošević, V.,& Filipović R., M.. (2018). Anti-aging properties of protein persulfidation. in Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences : from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia
Belgrade: Serbian Physiological Society., 143.
https://hdl.handle.net/21.15107/rcub_ibiss_5926

Živanović J, Kouroussis E, Miler M, Schott-Roux S, Jarić I, Jakovljević V, Milošević V, Filipović R. M. Anti-aging properties of protein persulfidation. in Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences : from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia. 2018;:143.
https://hdl.handle.net/21.15107/rcub_ibiss_5926 .

Živanović, Jasmina, Kouroussis, Emilia, Miler, Marko, Schott-Roux, Sonia, Jarić, Ivana, Jakovljević, Vladimir, Milošević, Verica, Filipović R., Miloš, "Anti-aging properties of protein persulfidation" in Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences : from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia (2018):143,
https://hdl.handle.net/21.15107/rcub_ibiss_5926 .